Coffee: Drink More, Live Longer

With origins in Ethiopia, coffee is now grown all around the world. Coffee lays claim to a $40 billion industry in the US. That’s a single food item! More than 50% of the US population drinks at least one 8 ounce coffee each day. Many people have several cups each day, but do they drink too much? Are they becoming dependent upon coffee? Are they immune to its acute effects? Should they care if they are?

coffeeAs we all know, most coffee drinkers do so to get a little pep in their step in the morning. Caffeine that is in the coffee is very well studied and comes with numerous benefits. Unfortunately (in this case), the body is extremely adaptive. We can become immune to the stimulatory effects elicited by caffeine, to the point where we need more and more coffee to get enough caffeine to wake us.

This effect is known as desensitization. And it happens with a wide range of things: cocaine, methamphetamine, and other illicit drugs; insulin (eventually becoming type II diabetes);and penicillin to name a few. While desensitization is never welcome, it is a sign that you should back away from coffee for a couple of days to a week an allow. It can even be an indicator of an even more serious issue; adrenal fatigue.

However great the acute stimulatory effects of coffee are the other chronic health benefits are much greater! Few know that coffee can be considered a superfood itself, on par with spinach, kale, and many other antioxidant, vitamins, and mineral rich foods.

Various other marketing-labeled superfoods.

Caffeine is much more than just a stimulant; it’s a cognitive enhancer, a metabolic booster, a gastrointestinal motivator (morning poop?), acts as an anti-inflammatory, improves fat burning, and improves athletic performance (1-8)! That’s JUST caffeine. Coffee also has a bunch of other bountiful compounds such as chlorogenic acid (nothing to do with chlorine!), various diterpenes, and several micronutrients(9).

A few coffee compounds.

While there are numerous healthful compounds in coffee, it can be hard to isolate which effects are explicitly attributed to each compound in the coffee matrix. This is in large part because most compounds behave or are absorbed/metabolized differently depending on what else is ingested at the same time. A similar effect is seen in fruit; the fructose in fruit is not considered nearly as detrimental compared to pure fructose because of the vitamins, minerals, fiber, and water that come along with the fructose in the fruit. Instead of focusing on the individual components, we’ll look at the whole of coffee and its potential positive and negative effects.

If you suffer from postprandial bloat (after eating bloat) from undigested foods, then you might be able to benefit from the gastric acid promoting effects of coffee (30). A cup of coffee has been compared to a 1,000 calorie meal in terms of how much it stimulates the gastrointestinal system to push food through. Despite that, it has been shown that coffee consumption does slow gastric emptying, this could be attributed to a higher (more basic) pH since coffee isn’t nearly as acidic as the stomach, which does slow the breakdown of food. This sound contradictory, and it is, in part. Increased gastric acid improves the breakdown of food. Increased gastric emptying literally corresponds to how quickly food is pushed through the intestines. Food that has not been broken down can pass through the intestines. On the other hand, food that is entirely broken down can remain in the intestines if gastric emptying is next to nothing. Neither is good and we want a balance between the two so we can vacate our bowels and still gets the essential nutrients from the foods we eat.

Diabetes is one of the fastest growing, and most expensive, ailments in the modern world. Coffee might have something to say about that, when a better overall nutritional approach is also adopted. Numerous studies have shown an inverse relationship between moderate coffee consumption and the development of type II diabetes mellitus! The largest studies (of more 120,000 people) showed that those who consumed 5 cups of coffee per day were correlated with a 54% lower risk of developing type II diabetes compared to those who drank no coffee (10). A more aggressive Finnish study showed that a whopping 10 cups of coffee each day led to a 79% lower incidence of type II diabetes (11)! I must say, that this is a LOT. Too much for most people because of the risk of hypertension and anxiety at such extremes. From the larger study, it was also found that only increasing caffeine produced a more modest inverse effect with the development of type II diabetes and decaffeinated coffee has even lesser effects; another example of the benefits of the entire matrix of coffee, not any one particular component.

There are numerous proposed mechanism as to WHY coffee reduces incidence of type II diabetes. A few are as a follows… Lowered glucose absorption in the intestines from chlorogenic acid and other phenolic, antioxidant compounds (12). Enhanced uptake of magnesium (13,14). Increased activity, energy expenditure, and subsequent weight loss (11,15,16).

Could coffee be THE anti-Parkinson's drug? It does support cognitive function; a lack of which is a large contributor to the development of Parkinson's Disease.
Could coffee be THE anti-Parkinson’s drug? It does support cognitive function; a lack of which is a large contributor to the development of Parkinson’s Disease.

Yet another disease affecting more and more people each year is Parkinson’s Disease. Again, coffee consumption has been correlated with reduced risk and later onset of Parkinson’s Disease (17). A study of 8,000 plus Japanese-Americans revealed that those who did NOT drink coffee were three to five times more likely to develop Parkinson’s in contrast to drinking three to four cups each day over a 10 year period (18). Unfortunately, there have been very mixed outcomes for postmenopausal women on estrogen replacement therapy (19). This has been attributed to the inhibitory effects of estrogen on a specific hepatic enzyme (CYP1A2) responsible for caffeine metabolism (20).

Possibly even more intriguing is the relationship between coffee and hepatocellular carcinoma (liver cancer). A large Japanese study in excess of 90,000 men and women over the 10 years revealed a inverse correlation between coffee consumption and liver cancer; more coffee, less incidence of liver cancer (21). Researchers found that 5 or more cups of coffee a day reduced risk by 76% over those who did not drink any coffee (22). These results are, in large part, attributed to two diterpenes  found in coffee and coffee oil; cafestol and kahweol. These two have demonstrated increases in liver enzyme levels (AST and ALT) (23). This is generally NOT a good thing. However, they have also shown to promote effective enzyme activity along with increases in hepatic glutathione and decreased DNA alterations resulting from carcinogens (in animals) (24,25). These showings are powerful in reducing abnormal liver functions.

With all of the benefits of coffee, there are also things to be weary of. A major complaint from coffee drinkers is acid reflux. It is acidic and does promote gastric acid production; both down and up stream. Be careful not to consume so much that it tends to come back up! Coffee has also been shown to inhibit iron and zinc absorption to a significant degree (26,27). In addition, caffeine is a potent vasoconstrictor, leading to increased blood pressure (hypertension) (28). However, a contrast function of caffeine is diuresis which is often used as a mode to reduce blood pressure (29). Next it should be noted that everyone has different sensitivity to all foods and chemicals, including coffee and caffeine. As a result, you should assess your own tolerance of caffeine and coffee. Perhaps you can consume 5 or more cups and feel great, but others might consume the same amount and be brought to the edge of an anxiety attack with sky high blood pressure. We are all different!


If you love coffee, then this review may be your best friend to encourage you to drink a bit more without worry. If you don’t, then you’ve now been made aware of what you could be missing out on. Either way, coffee won’t kill you nor make you immortal. It might be able to improve your quality of life to a point by reducing risk of type II diabetes and liver cancer, improving your cognition and athletic performance, and even reduce total body inflammation while improving digestion because of the phenolics, plant-based compounds within these magical Ethiopian beans. Of course, the quality of your coffee is important, like the quality of your food, so do your due diligence and treat coffee with the respect it deserves and get some of the good stuff. In addition to coffee and caffeine, you can also benefit from the wonders of cocoa powder! These are small additions to your lifestyle that could very well enhance your total sense of well-being and quality of life. That said, there is no cure all above and beyond proper, well-balanced nutrition and exercise on a regular basis. Coffee may be beneficial, but it won’t counteract a lifestyle of poor eating decisions.


  1. Nehlig A, Daval JL, Debry G (1992). “Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects”. Brain Res. Brain Res. Rev. 17 (2): 139–70. doi:10.1016/0165-0173(92)90012-B. PMID 1356551.
  2. Smith A (2002). “Effects of caffeine on human behavior”. Food and Chemical Toxicology 40 (9): 1243–55. doi:10.1016/S0278-6915(02)00096-0. PMID 12204388.
  3. Koot P, Deurenberg P (1995). “Comparison of changes in energy expenditure and body temperatures after caffeine consumption”. Annals of Nutrition and Metabolism 39 (3): 135–42. doi:10.1159/000177854. PMID 7486839.
  4. Cohen S, Booth GH (1975). “Gastric acid secretion and lower-esophageal-sphincter pressure in response to coffee and caffeine”. The New England Journal of Medicine 293 (18): 897–9. doi:10.1056/NEJM197510302931803. PMID 1177987.
  5. Boekema PJ, Samsom M, Van Berge Henegouwen GP, Smout AJ (1999). “Coffee and gastrointestinal function: Facts and fiction. A review”. Scandinavian journal of gastroenterology 230 (230): 35–9. PMID 10499460.
  6. Pesta DH, Angadi SS, Burtscher M, Roberts CK (2013). “The effects of caffeine, nicotine, ethanol, and tetrahydrocannabinol on exercise performance”. Nutr Metab (Lond) 10 (1): 71. doi:10.1186/1743-7075-10-71. PMC 3878772. PMID 24330705.
  7. Peters-Golden M, Canetti C, Mancuso P, Coffey MJ. (2005). “Leukotrienes: underappreciated mediators of innate immune responses”. Journal of Immunology 174 (2): 589–94. doi:10.4049/jimmunol.174.2.589. PMID 15634873.
  8. “Caffeine”. The Pharmacogenetics and Pharmacogenomics Knowledge Base. Retrieved 25 October 2010
  9. Higdon JV., Frei B., (2006), “Coffee and health: a recent review in human research.” Crit Rev Food Sci Nutr. 2006;46(2):101-23. PMID: 16507475
  10. Salazar-Martinez , E. , Willett , W. C. Ascherio , A. 2004. Coffee consumption and risk for type 2 diabetes mellitus. Ann. Intern. Med., 140: 1–8. [PUBMED][INFOTRIEVE][CSA] [CrossRef], [PubMed], [Web of Science ®]
  11. Tuomilehto , J. , Hu , G. and Bidel , S. 2004. Coffee consumption and risk of type 2 diabetes mellitus among middle-aged Finnish men and women. JAMA., 291: 1213–1219. [PUBMED][INFOTRIEVE][CROSSREF][CSA]
  12. Welsch , C. A. , Lachance , P. A. and Wasserman , B. P. 1989. Dietary phenolic compounds: Inhibition of Na+-dependent D-glucose uptake in rat intestinal brush border membrane vesicles. J. Nutr., 119: 1698–1704. [PUBMED]
  13. Meyer , K. A. , Kushi , L. H. Jacobs , D. R. Jr. 2000. Carbohydrates, dietary fiber, and incident type 2 diabetes in older women. Am. J. Clin Nutr., 71: 921–930. [PUBMED]
  14. Lopez-Ridaura , R. , Willett , W. C. Rimm , E. B. 2004. Magnesium intake and risk of type 2 diabetes in men and women. Diabetes Care., 27: 134–140. [PUBMED]
  15. Horton , T. J. and Geissler , C. A. 1996. Post-prandial thermogenesis with ephedrine, caffeine and aspirin in lean, pre-disposed obese and obese women. Int. J. Obes Relat Metab Disord., 20: 91–97. [PUBMED]
  16. van Dam , R. M. and Feskens , E. J. 2002. Coffee consumption and risk of type 2 diabetes mellitus. Lancet., 360: 1477–1478. [PUBMED]
  17. Hernan , M. A. , Takkouche , B. Caamano-Isorna , F. 2002. A meta-analysis of coffee drinking, cigarette smoking, and the risk of Parkinson’s disease. Ann. Neurol., 52: 276–284. [PUBMED]
  18. Ross , G. W. , Abbott , R. D. Petrovitch , H. 2000. Association of coffee and caffeine intake with the risk of Parkinson disease. JAMA., 283: 2674–2679. [PUBMED]
  19. Ascherio , A. and Chen , H. 2003. Caffeinated clues from epidemiology of Parkinson’s disease. Neurology., 61: S51–S54. [PUBMED]
  20. Pollock , B. G. , Wylie , M. Stack , J. A. 1999. Inhibition of caffeine metabolism by estrogen replacement therapy in postmenopausal women. J. Clin. Pharmacol., 39: 936–940. [PUBMED]
  21. Inoue , M. , Yoshimi , I. , Sobue , T. and Tsugane , S. 2005. Influence of coffee drinking on subsequent risk of hepatocellular carcinoma: A prospective study in Japan. J. Natl. Cancer Inst., 97: 293–300. [PUBMED]
  22. Shimazu , T. , Tsubono , Y. Kuriyama , S. 2005. Coffee consumption and the risk of primary liver cancer: Pooled analysis of two prospective studies in Japan. Int. J. Cancer., 116: 150–154. [PUBMED]
  23. Urgert , R. , Essed , N. van der Weg , G. 1997. Separate effects of the coffee diterpenes cafestol and kahweol on serum lipids and liver aminotransferases. Am. J. Clin Nutr., 65: 519–524. [PUBMED]
  24. Cavin , C. , Holzhaeuser , D. Scharf , G. 2002. Cafestol and kahweol, two coffee specific diterpenes with anticarcinogenic activity. Food Chem. Toxicol., 40: 1155–1163. [PUBMED]
  25. Huber , W. W. , Scharf , G. Rossmanith , W. 2002. The coffee components kahweol and cafestol induce gamma-glutamylcysteine synthetase, the rate limiting enzyme of chemoprotective glutathione synthesis, in several organs of the rat. Arch. Toxicol., 75: 685–694. [PUBMED]
  26. Morck , T. A. , Lynch , S. R. and Cook , J. D. 1983. Inhibition of food iron absorption by coffee. Am. J. Clin. Nutr., 37: 416–420. [PUBMED]
  27. Van Dyck , K. , Tas , S. , Robberecht , H. and Deelstra , H. 1996. The influence of different food components on the in vitro availability of iron, zinc and calcium from a composed meal. Int. J. Food Sci. Nutr., 47: 499–506. [PUBMED]
  28. Nurminen , M. L. , Niittynen , L. , Korpela , R. and Vapaatalo , H. 1999. Coffee, caffeine and blood pressure: a critical review. Eur. J. Clin. Nutr., 53: 831–839. [PUBMED]
  29. Modulation of adenosine receptor expression in the proximal tubule: a novel adaptive mechanism to regulate renal salt and water metabolism Am. J. Physiol. Renal Physiol. 1 July 2008 295:F35-F36
  30. Boekema PJ., et al., “Coffee and gastrointestinal function: facts and fictions. A review.” Scand J Gastroenterol Suppl. 1999;230:35-9.[PUBMED]

The Chocolate Fountain of Youth

Unopened cacao pods and fermented cocoa beans.

The day has arrived; you’ve hoped and prayed that this day would come. The day that someone tells you, legitimately, that chocolate is good for your health. And it is! However, I wouldn’t go out gorging on chocolate bars. The amounts of added fats and sugars to a vast majority of chocolate bars is going to far negate the positive effects of the compounds found within the cocoa that gives chocolate its distinguished taste. Continue reading The Chocolate Fountain of Youth

Ladies: Why You Should Resistance Train, Pt. 2 Hormones

It’s that time of the month again. Hormones are wildly fluctuating as the female body goes through a routine, albeit troublesome, cycle; menstruation. While the menstrual cycle is the butt of many jokes, it is quite serious business. Especially when it comes to hormones and maintaining sanity.

I’ll admit it. Hormonal regulation from resistance training benefits everyone, not just women, but it’s always promising to hear of something that might alleviate some wackiness.

In part 1 of this series, I discussed the benefits of resistance training in terms of bone health and muscle strength. After only 10 weeks of a moderate volume training regime, three time per week, elderly women were able to maintain bone health while increasing muscular strength. This may not seem all that significant, but as we age it becomes harder to move our bodies effectively leading to falls and other mishaps; both of which are the result of less motor (muscular) control and weakened bones.

This time around, it’s all about hormones! Whether it’s raising testosterone or keeping cortisol at a lower, steady level the benefits and effects of hormonal variances resulting from resistance training will keep you younger, stronger, and less anxious or stressed out.

Before any specifics, I would like to point out the major differences in males and females when it comes to hormonal production; tests and ovaries. Both women and men produce testosterone and estrogen, the primary sex hormones, along with a plethora of other hormones. Women do produce larger amounts of estrogen and progesterone with less testosterone when compared to men. That said, we still all produce the hormones.

While I’d love to be able to say that resistance training stabilizes estrogens and reduces their variability throughout the menstrual cycle, I can’t. In fact, there is very little evidence to show how resistance training and estrogen might be acutely and chronically related. (1) Unfortunately, the estrogenic effects that come into play for women throughout the month are hard to attenuate, or even predict for some females. Many of these include increased body fat and subsequent weight gain, cyclic migraines, fluid retention, anxiety, and poor sleep; none of which are good. But many of which can be counterbalanced by a stabilization and enhancement of other hormones such as testosterone and cortisol that results from resistance training.

Most women (and subsequently men) know that hormones absolutely fluctuate during the menstrual cycle; that’s not going to change to a large extent. At least, not by exercise. And it probably shouldn’t be adjusted to any large extent for a variety of biological reasons.


The graph at right depicts, relatively, the variations of hormones changing during the menstrual cycle. As you can see, as the follicular period ends and the luteal phase begins, estradiol begins to drop with an associated spike in LH (lutenizing hormone). LH is a key factor telling the body to produce larger amounts of testosterone; which comes with more aggression and impulsive reactions.

Now that some poor news is out of the way, I’d like to focus on what resistance training has shown to be able to do to help us! Since science attempts to be unbiased, to a degree, there isn’t a huge selection of data focusing solely on women weight training, but there are some that I’d like to make the center of the conversation a bit later on.

We’ll begin big and broad.

Again, of all the literature out there, the number of studies focusing on women and acute testosterone responses post-exercise are few. However, Nindhl et al. demonstrated a great 25% increase in free testosterone in women after a high volume squat workout (2). It shouldn’t be surprising to know that there’s plenty of research to support the benefits of large muscle mass exercises (i.e squats, jumps, deadlifts, cleans) for both women and men. Unfortunately, a review by Hakkinen, Pakarinen, and Kraemer did not find an increase in free testosterone for middle-age and elderly women (3). This may, in part, be attributed to different levels of estrogens, which are potent inhibitors of testosterone production (via negative feedback) (4). A more detailed description of exercise intensity, volume, and load and their effect on changes in testosterone are laid-out splendidly below, by Kraemer and Ratamess.


Taken from Further Reading 1: Kraemer and Ratamess review.

Since a vast majority of people do not exercise on a regular basis, a much more significant portion of studies focus on the general population, or untrained persons. However, there is evidence to support the fact that in younger persons the more trained an individual is, to an extent, the greater the (positive) response to hormones from exercises(5-8)! So you better get started sooner rather than later.

Now, hopefully, you haven’t zoned out after some testosterone talk. Testosterone is vitally important for all people, not just men! Without testosterone and some of its precursors, such as DHEA and androstenedione, the female body is unable to produce sufficient amounts of estrogens (9) After menopause, when testosterone production halts, the body uses adipose (fat) tissues to create estrogen in women; a major factor driving fat gain in postmenopausal women: the body needs estrogen and it must get it from somewhere.

But without testosterone, you’ll also miss out on a LOT of its benefits: improved mood, increased fat oxidation (loss), increased strength, bone mineral density maintenance, and better sleep. Oddly enough, these effects are the polar opposite of the effects of increased and varied estrogen mentioned earlier. Estrogen and testosterone are the primary drivers which differentiate the genders of the human species. Our biochemistry and structure support the variances in these sex hormones to a very large degree. These changes are also enhanced or amplified by the varied amounts of these two hormones and their analogs (cousins). That’s enough rambling about testosterone. It’s important, in the right amounts, just as estrogen is.

There’s another crucial hormone which should, for the most part, also remain at static levels in the body: cortisol.

I love (the idea of) cortisol. It is incredibly under-appreciated in its effects in our lives and how it affects our bodies.

Cortisol is known as the stress hormone. You’ve likely seen television commercials

Spouting fat loss pills that proclaim to abolish cortisol to the underworld. And for good reason. While I can’t speak for the efficacy of those things, I can attest to the woes that chronic increased cortisol brings. Our bodies are unable to differentiate between physical, psychological, and physiological stress. It just knows stress.

Effects elicited by increased cortisol levels,

Cortisol is produced by the adrenal cortex, which is also a major player in the flight-or-fight response. When the body is stressed, it reacts by dumping cortisol, dopamine, and serotonin  and other molecules into the body. Dopamine and serotonin are neurotransmitters. These substances allow more, thus faster, connections between neurons in the brain increasing alertness and the ability to react while inhibiting sleep (insomnia, anyone?); something critical in dire circumstances. This is great when used sparingly. However, when overdone, there are repercussions. Increased cortisol levels direct the body to storage energy (food) for later (as adipose tissue) particularly around the internal organs (in the belly). This visceral fat is extremely harmful when it gets out of hand because it can steal nutrients from (getting to) internal organs, essentially starving them, and suffocating them as the fat grows. In addition, increased cortisol levels affect ghrelin and leptin; the hunger hormones (though they do much more). Ghrelin and leptin affected in a way which increases appetite.

I’ve said very little relating cortisol to exercise though. Partially because exercise acutely increases cortisol levels. Cortisol, as I mentioned, can be nasty and is even catabolic (muscle wasting/eating). The nastiness of cortisol comes about due to chronically elevated levels. The acute effect from exercise is the result from stimulation of the adrenals (fight-or-flight response).

As a quick aside…If you’re constantly stressed, then you likely crave carbohydrates, which suppress cortisol production.

The true benefit of exercise with regards to cortisol comes over the long term. Exercise has been shown to modify the glucocorticoid receptors in the body, particularly in skeletal muscle, making the binding and effectiveness of cortisol to be greatly reduced (10). In parallel, the amount of cortisol produced from exercise is also reduced in the long term, while neurotransmitters like dopamine and serotonin are continued to be produced. These phenomena are attributed to the relaxed feeling after strenuous exercise, also known as a runner’s high in endurance athletes.

By reducing the cortisol that binds to glucocorticoid receptors, the effects of cortisol are inhibited to a safe extent. This results in less muscle breakdown over time, a decreased feeling of anxiety, a more satiated appetite, the ability to sleep soundly, and a healthier body from less visceral fat in your midsection. Only a couple of things that might interest you.

This post is getting to be lengthy, so I’d like to stop it here in order to not overwhelming anyone further. If you’d like to know some more, then please feel free to begin some discussion in the comments or check out the references section!

Whether you choose to strength train to looked better or feel better, you will absolutely be healthier!

Hormonal stabilization is just another benefit of resistance exercise for women. Our previous article focused on strength and bone mineral density, specifically in older ages, but we’ve traversed into a topic that affects all ages and is particularly important for young to middle-aged women because of the hormonal effects of the menstrual cycle wreaking havoc on a monthly basis. With the help of proper resistance training, you might be able to attenuate some of those nasty effects by regulating both testosterone and cortisol which greatly impact the mood and overall well being of a person whose estrogen and estrogenic hormones are rising and falling.



  1. Sports Med 2005; 35 (4): 339-361
  2. Int J Sport Nutr Exerc Metab 2001; 11: 461-465
  3. J Gerontol A Biol Sci Med Sci 2000; 55: B95-105
  4. J Clin Endocrinol Metab 2000;85:3027–35
  5. (Kraemer WJ, Fry AC, Warren BJ, et al. Acute hormonal responses in elite junior weightlifters. Int J Sports Med 1992; 13: 103-9
  6. Craig BW, Brown R, Everhart J. Effects of progressive resistance training on growth hormone and testosterone levels in young and elderly subjects. Mech Ageing Dev 1989; 49:159-69
  7. Nindl BC, Kraemer WJ, Gotshalk LA, et al. Testosterone responses after resistance exercise in women: influence of regional fat distribution. Int J Sport Nutr Exerc Metab 2001; 11:451-465
  8. Cumming DC, Wall SR, Galbraith MA, et al. Reproductive hormone responses to resistance exercise. Med Sci Sports Exerc 1987; 19: 234-8
  10. Willoughby DS, Taylor M, Taylor L. Glucocorticoid receptor and ubiquitin expression after repeated eccentric exercise. Med Sci Sports Exerc 2003; 35: 2023-31
  11. Additional References: Hayes FJ, Seminara SB, Decruz S, Boepple PA, Crowley F. Aromatase inhibition in the human male reveals a hypothalamic site of estrogen feedback. J Clin Endocrinol Metab 2000;85:3027–35.
  12. Bagatell CJ, Dahl KD, Bremner WJ. The direct pituitary effect of testosterone to inhibit gonadotropin secretion in men is partially mediated by aromatization to estradiol. J Androl 1994;15:15–21
  13. Finkelstein JS, O’Dea LS, Whitcomb RW, Crowley WF. Sex steroid control of gonadotropin secretion in the human male. II. Effect of estradiol administration in normal and gonadotropin-releasing hormone-deficient men. J Clin Endocrinol Metab 1991;73:621–8.
  14. Veldhuis JD, Dufau ML. Estradiol modulates the pulsatile secretion of biologically active luteinizing hormone in man. J Clin Invest 1987;80:631–8.
  15. Schnorr JA, Bray MJ, Veldhuis JD. Aromatization mediates testosterone’s short-term feedback restraint of 24-h endogenously driven and acute exogenous gonadotropin-releasing hormone-stimulated luteinizing hormone and follicle-stimulating hormone secretion in young men. J Clin Endocrinol Metab. 2001 Jun;86(6):2600-6.
  16. Bluher, M., Importance of estrogen receptors in adipose tissue function. Mol Metab. 2013 Aug; 2(3): 130–132. doi:10.1016/j.molmet.2013.07.001
  17. Gambacciani M., Ciaponi M., Cappagli B., Piaggesi L., De Simone L., Orlandi R., Genazzani A.R. Body weight, body fat distribution, and hormonal replacement therapy in early postmenopausal women. Journal of Clinical Endocrinology and Metabolism. 1997;82:414–417.


Great Further Readings:


FOOD: Causing Inflammation and Depression?

Oreos and Ho-Hos and Twinkies! Oh my! They definitely bring inflammation. They may also bring temporary mental relief, but they might be the cause of your down-in-the-dumps attitude and outlook in the first place. Continue reading FOOD: Causing Inflammation and Depression?

Resistant Starch: The Greatest, Unknown Nutrient?

If you’ve tried to get a grip on your nutrition, then it’s a certainty resistant starchthat you know what macronutrients are; proteins, carbohydrates and fats. You’ve also looked at the back of a package to peak at the Nutrition Facts. Within fats and carbohydrates, there are certain types. Saturated, monounsaturated, polyunsaturated, and trans fats come to mind along with types of complex and simple for carbohydrates. There’s another type of carbohydrate that you likely haven’t heard a peep about; resistant starch. Continue reading Resistant Starch: The Greatest, Unknown Nutrient?

The Vitamin A and D Conundrum

The Vitamin A and D Conundrum

VitaminsBy Alden Ryno

The fact that you’re reading this on the Mountain Dog site means that you probably take a variety of vitamins and supplements throughout the day. You likely have specific reasons why you take some of them while others are thrown in because “you should” take them or they are along for the ride with your multivitamin. A vitamin that has really gained momentum in past years is Vitamin D, and for great reasons! Vitamin D participates in numerous bodily functions ranging from bone growth and health to protecting against depression and promoting proper β-cell function which results in enhanced insulin sensitivity.1-4 Despite decades of research concerning the functions of vitamin D research, there are still profound benefits being discovered today. In fact, Rhonda Patrick and Bruce Ames recently published data in February of 2015 showing a causal link between proper levels of Vitamin D and serotonin production affecting the development of autism in children.5,6 However, in our supplement crazed society, we are more concerned with the individual actions of one supplement rather than the interactions between distinct nutrients. Just like pharmaceutical drug interactions, we should be keenly aware of how the vitamins and supplements we ingest interact with one another. Here, we’ll take a look at vitamin A and vitamin D alone, and then in tandem in order to see what may happen between them and why we should care.

Our Essential Friends

Vitamin D comes in two primary forms: Vitamin D2 (ergocalciferol) and Vitamin D3 (cholecalciferol). Cholecalciferol is the form which is found in animal tissue and is synthesized in our skin through direct sunlight from provitamin D (7-dehydrocholesterol). Ergocalciferol is the plant-based form of Vitamin D. Throughout the body, both D2 and D3 are treated quite similarly, though D3 is more easily converted to active forms of Vitamin D in the body.7

Advanced-Nutrition-2015-03-1Vitamin D is absorbed in the jejunum and ileum portions of the small intestines via passive diffusion.8 Like many other vitamins, our bodies don’t use the ingested versions of Vitamin D, but converts the two into the active form(s) of Vitamin D, 1,25-dihydroxyvitamin D, or calcitriol, through two enzymatic hydroxylations in the liver and then the kidneys.9,10 Calcitriol then travels throughout the blood stream bound to Vitamin D binding proteins (VBP) where it travels to the parathyroid or various other Vitamin D Receptor (VDR) sites, which are still under investigation.11-13 Vitamin D acts as a hormone (signaling molecule) throughout the body and is a vital regulator in nutrient absorption during digestion and in calcium and phosphate concentrations in bones through restriction of the parathyroid to produce parathyroid hormone (PTH).12,14 When serum levels of Vitamin D are low, the body is signaled to pull calcium from the bones and into the blood stream due to high levels of PTH. This results in acute hypercalcemia in the blood and may lead to kidney stones.12,16 This may also result in osteoporosis if unaddressed over a long period of time.

Advanced-Nutrition-2015-03-2A diet rich in orange plant-based foods will almost certainly provide adequate amounts of vitamin A in the form of provitamin A, or carotenoids (β-carotene, β-cryptoxanthin, etc). These compounds are poorly converted into various types of active and preformed vitamin A (retinol, retinyl esters, and retinoic acid).16 Animal sources such as liver provide much more potent and active quantities of vitamin A. It’s unlikely that you don’t get enough vitamin A from your diet and a multivitamin, since a MV generally supplements with the active molecules of vitamin A. 16,17 Like vitamin D, vitamin A is absorbed via lipophilic micelles in the small intestine, however, it is thought that Vitamin A is absorbed via facilitated diffusion.18


So what does vitamin A do? It is essential in proper retina function in the eye; hence the name retinol. It is also a largely responsible for the growth and differentiation of epithelial cells which make up the linings of cavities in the body from the intestines to the lunges and even the eyes.16,19 A third, but lesser researched function associated with vitamin A is insulin resistance. As the transporter of vitamin A (retinol binding protein [RBP]) rises, there is a decrease in glucose transporter type 4 (GLUT4) activity and insulin sensitivity.21 These three functions, though not the only factors, clearly demonstrate the significance of vitamin A. A select few of the symptoms of hypervitaminosis A (HVA) include bone fragility, potential liver distress and disease, and increased insulin resistance.16,20,21

Who beats whom?

Interestingly enough, the first and last of those symptoms are opposites of sufficient amounts of Vitamin D. Is there an interaction between these two fat-soluble vitamins? You betcha!

The antagonistic relationship between vitamins A and D has been intriguing scientists as early as 1985 when researchers at the University of Minnesota looked into the skeletal development of turkeys. Metz, et al, found that a diet high in vitamin A and normal in vitamin D exhibited symptoms of HVA (depressed growth, impaired mobility, and weak bones) while a diet normal in vitamin A and high in vitamin D displayed only mild symptoms of heightened levels of serum vitamin D (25-hydroxycholecalciferol) such as kidney stones from elevated calcium levels.22 However, turkeys fed a diet high in both vitamins A and D were similar to turkeys fed a control diet with normal levels of vitamins A and D. This tells us that there is a point at which the vitamins essentially nullify the effects of each other. Why is that? And what are the optimal intakes for each vitamin in order to benefit from both?

We discussed that both vitamin A and D are absorbed in the small intestine and there does not appear to be any evidence to support that the vitamins interfere with one another at this level, especially since they are absorbed through different means. Let’s dig deeper into the body to see what is happening.

Once converted to their active forms via enzymes from the same family of enzymes, cytochrome P450, they bind to specific protein-based receptor sites. Vitamin A binds to retinoic acid receptors (RARs) and retinoid X receptors (RXRs); the “X” refers to any number of retinol analogs including retinoic acid, retinal, retinol, and retinyl esters. 23,24 Vitamin D binds to vitamin D receptors (VDRs) and retinoid X receptors (RXRs). We can already see that both vitamins share a common receptor in the RXRs. However, the location on the RXRs where each vitamin binds are different, and with distinct affinities (how tightly they bind).25

While vitamin D can perform many of its actions by only binding to VBPs in the blood, several other functions require a heterodimer between VDRs and RXRs in order for gene expression to occur.23,24 This is where vitamin A begins to cause problems with the actions of vitamin D. As the name suggests, retinoid X receptors preferentially bind to vitamin A analogs compared to vitamin D by more than 2 orders of magnitude. This means that when surplus vitamin A is present, it decreases the number of receptors available for vitamin D. Even though vitamin A and vitamin D bind to different locations on the receptors, the action of binding to one alters the shape of the receptor; inhibiting the binding of other molecules. This is known as allosteric competitive inhibition. While vitamin D can bind to VDRs in the presence of excess vitamin A, it is impossible for gene expression to occur without the dimeric duo of vitamin D bound VDRs and RXRs. As a result, the vitamin D-VDR complexes are metabolized and discarded before any free RXRs are available to bind.

Take note that this occurs only in the presence of excess vitamin A. It appears that there are plenty of RXRs to satisfy both vitamin A and vitamin D when levels of vitamin A are not elevated. However, the previous inhibitory mechanism may be partially overridden with an ample amount of vitamin D and vitamin A, despite the fact that vitamin A preferentially binds to the RXRs.

The previous paragraph tells us that a diet with normal levels of vitamin A and high amounts of vitamin D will produce the benefits of both vitamins. Meanwhile, a diet normal in both or high in vitamin A will negate many of the positive effects of vitamin D. As a result, it is recommended that a diet should be supplemented with vitamin D, but not so for vitamin A. This is assuming that the diet has enough foods containing carotenoids (orange foods). If not, then small amounts of vitamin A should be supplemented, preferably in the form of beta-carotene, not retinol and its analogs.16

How to Get the Best of Both Worlds

According to the NIH, the RDA for vitamin A in the form of retinol is 900 IU (equal to 900 RE [retinol equivalents] or 900 mcg retinol) and roughly 10,000-20,000 IU from β-carotene or β-cryptoxanthin. The RDA varies greatly due to the wide range of conversion from plants to retinol in the body; anywhere from 12:1 to 24:1, depending on the carotenoid source.16 For example, a normal sweet potato (~8oz/227g) provides nearly 28,000 IU of vitamin A from beta-carotene (2,300 RE). A proper diet should supply sufficient amounts of Vitamin A and supplementation further is not recommended, if you seek the benefits of supplemental vitamin D. Vitamin D, on the other hand, is hard to get from the diet, but is bountiful with 20-30 minutes of unprotected exposure to the sun, in the summer months. The RDA for vitamin D is quite low at a meager 200-600 IU for 19-50 year old adults.7 Despite that, recent research, including that of Dr. Rhonda Patrick, have warranted a significant rise in the RDA. Dr. Patrick has proposed intakes as great as 40 IU/lb (88 IU/kg or 1000 IU/25 lbs) of bodyweight for average weight adults. Her recommendations indicate an intake of up to 9,000 IU for a 225 pound male. She still recommends getting blood work done prior to such rigorous supplementation though. Optimal levels of serum vitamin D (25-dihydroxy-vitamin D) fall in the range of 20 ng/mL or 50 nmol/mL, but remain lower than 50 ng/mL or 125 ng/mL.7

To recap, we should be getting both vitamin A and D in our diet. However, we should also supplement with vitamin D (up to 1,000 IU per 25 pounds of bodyweight), especially during the winter months or when your exposure to direct sunlight is limited. I don’t believe that supplementing with vitamin A is necessary with proper diet and is even detrimental to effectively using supplemental vitamin D. If you do eat a lot of vitamin A rich foods (liver, sweet potatoes/yams, carrots, pumpkin, dark greens), then it is also advised to supplement with vitamin D in order to provide the body with plenty due to the antagonistic nature of vitamin A.

As our interests in our personal health continue to rise, we should aim to learn more about what we’re putting into our bodies. Only two nutrients were covered here while you (probably) take in dozens a day. Do you think that those other things aren’t interacting with one another? I’ll tell you now that they are. Not unlike pharmaceutical drugs, we should at least be cognizant of both antagonistic and synergistic interactions between vitamins, minerals, and any number of other supplements that we ingest. I hope that you gained a small insight into what you put into your body and you’ll be interested to learn and educate yourself further in the future.



  1. Cranney A, Horsley T, O’Donnell S, Weiler H, Puil L, Ooi D, Atkinson S, Ward L, Moher D, Hanley D, Fang M, Yazdi F, Garritty C, Sampson M, Barrowman N, Tsertsvadze A, Mamaladze V (August 2007). “Effectiveness and safety of vitamin D in relation to bone health”. Evidence report/technology assessment (158): 1–235. PMID 18088161.
  2. Shaffer JA, Edmondson D, Wasson LT, Falzon L, Homma K, Ezeokoli N, Li P, Davidson KW (2014).”Vitamin D Supplementation for Depressive Symptoms: A Systematic Review and Meta-Analysis of Randomized Controlled Trials”. Psychosomatic Medicine 76 (3): 190–6. doi:10.1097/psy.0000000000000044.PMID 24632894
  3. Kayaniyil S, Gerstein HC, Veith R, Perkins BA, Retnakaran R, Harris SB, Knight JA, Zinman B, Qi Y, H. A. (2010). Association of Vitamin D With Insulin Resistance and beta-Cell Dysfunction in Subjects at Risk for Type 2 Diabetes. Diabetes Care, 33(6), 1379–1381. doi:10.2337/dc09-2321.
  4. Mitri, J., Dawson-hughes, B., Hu, F. B., & Pittas, A. G. (2011). Effects of vitamin D and calcium supplementation on pancreatic b cell function , insulin sensitivity , and glycemia in adults at high risk of diabetes : the Calcium and Vitamin D for Diabetes Mellitus ( CaDDM ) randomized controlled trial 1 – 4. Am J Clin Nutr, 94(4), 486–494. doi:10.3945/ajcn.111.011684.1
  5. Rhonda P. Patrick, B. N. A. (n.d.). Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism. FASEB, 28(6), 2398–2413. doi:10.1096/fj.13-246546
  6. Rhonda P. Patrick, B. N. A. (n.d.). Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar, schizophrenia, and impulsive behavior. FASEB. doi:10.1096/fj.14-268342
  7. Gloth, F. M. (1995). Vitamin D. Lancet, 345, 1185.
  8. Hollander, D., Muralidhara, K. S., & Zimmerman, a. (1978). Vitamin D-3 intestinal absorption in vivo: influence of fatty acids, bile salts, and perfusate pH on absorption. Gut, 19(November 1977), 267–272. doi:10.1136/gut.19.4.267
  9. Blunt, J.W., DeLuca, H.F. & Schnoes, H.K. (1968). 25-hydroxycholecalciferol. A biologically active metabolite of vitamin D3. Biochem., 7: 3317-3322.
  10. 3. Fraser, D.R. & Kodicek, E. (1970). Unique biosynthesis by kidney of a biologically active vitamin D metabolite. Nature, 228: 764-766.
  11. Rochel, N., Wurtz, J. M., Mitschler, a, Klaholz, B., & Moras, D. (2000). The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand. Molecular Cell, 5, 173–179. doi:10.1016/S1097-2765(00)80413-X
  12. Bikle, D. (2009). Nonclassic actions of vitamin D. Journal of Clinical Endocrinology and Metabolism, 94(January 2009), 26–34. doi:10.1210/jc.2008-1454
  13. Wang, Y., & DeLuca, H. F. (2011). Is the vitamin D receptor found in muscle? Endocrinology, 152(March), 354–363. doi:10.1210/en.2010-1109
  14. Jones, G., Strugnell, S. a, & DeLuca, H. F. (1998). Current understanding of the molecular actions of vitamin D. Physiological Reviews, 78(4), 1193–1231.
  15. Cranney A, Horsley T, O’Donnell S, Weiler H, Puil L, Ooi D, Atkinson S, Ward L, Moher D, Hanley D, Fang M, Yazdi F, Garritty C, Sampson M, Barrowman N, Tsertsvadze A, M. V. (n.d.). Effectiveness and safety of vitamin D in relation to bone health. Retrieved from
  16. Vitamin A. (n.d.). FAO/WHO Expert Consultation on Human Vitamin and Mineral Requirements, 87–107.
  17. Chen, W., & Chen, G. (2014). The Roles of Vitamin A in the Regulation of Carbohydrate, Lipid, and Protein Metabolism. Journal of Clinical Medicine, 3, 453–479. doi:10.3390/jcm3020453
  18. Dew, S.E.; Ong, D.E. (1994). Specificity of the retinol transporter of the rat small intestine brush border. Biochemistry, 33, 12340–12345.
  19. Ackerley, S. K. Developlmental Biology Online. “Epithelial cells”. 09 Dec 2005. 04 Sept 2010
  20. Aburto, a, Edwards, H. M., & Britton, W. M. (1998). The influence of vitamin A on the utilization and amelioration of toxicity of cholecalciferol, 25-hydroxycholecalciferol, and 1,25 dihydroxycholecalciferol in young broiler chickens. Poultry Science, 77, 585–593.
  21. Qin Yang, Timothy E. Graham, Nimesh Mody, Frederic Preitner, Odile D. Peroni, Janice M. Zabolotny, Ko Kotani, Loredana Quadro & Barbara B. Kahn. (2005). Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature, 436, 356–362. doi:10.1038/nature03711
  22. Metz, a L., Walser, M. M., & Olson, W. G. (1985). The interaction of dietary vitamin A and vitamin D related to skeletal development in the turkey poult. The Journal of Nutrition, 115, 929–935.
  23. MacDonald, P. N., Dowd, D. R., Nakajima, S., Galligan, M. a, Reeder, M. C., Haussler, C. a, … Haussler, M. R. (1993). Retinoid X receptors stimulate and 9-cis retinoic acid inhibits 1,25-dihydroxyvitamin D3-activated expression of the rat osteocalcin gene. Molecular and Cellular Biology, 13(9), 5907–5917. doi:10.1128/MCB.13.9.5907.Updated
  24. Thompson, P. D., Jurutka, P. W., Haussler, C. a, Whitfield, G. K., & Haussler, M. R. (1998). Heterodimeric DNA Binding by the Vitamin D Receptor and Retinoid X Receptors Is Enhanced by 1 , 25-Dihydroxyvitamin D 3 and Inhibited by 9-cis-Retinoic Acid, 273(14), 8483–8491.
  25. Richard A. Heyman, David J. Mangelsdorf, Jacqueline A. Dyck, Robert B. Stein, Gregor Eichele, Ronald M. Evans, C. T. (1992). 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell, 68(2), 397–406. doi:10.1016/0092-8674(92)90479-V

Ladies: Why You Should Resistance Train, Pt. 1

Yes, this is intended explicitly for women. That doesn’t mean that men should lift weights either, but they don’t usually need much persuading.

You will not get big and bulky (unless you really try to do so). You will have more energy. You will be able to move more efficiently and effectively. You will feel better; both physically and mentally. Continue reading Ladies: Why You Should Resistance Train, Pt. 1

Fructose is NOT Your Friend.

Sugar is bad. Plain and simple. If you didn’t know that, then you do now, and it should be something that you remember ad infinitm. However, we’re under the impression that fructose is good for us. It’s not. And here, I’m going to explain why and back that up with some science. Continue reading Fructose is NOT Your Friend.

Your performance resource!

Powered by WishList Member - Membership Software