keto dhea and the ketogenic diet

Dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEA-S) are the most abundant circulating steroid hormones in humans.  However, the molecular, cellular, and physiological mechanism of its action and relationship to human health are not yet fully known.  What is known, however, is that large amounts of DHEA are produced during fetal development, but after birth, this production falls sharply and remains low for several years.  But then, the synthesis resumes and the levels of the hormones peak during the second decade of life.  However, by the third decade, an age-dependent decline in DHEA ensues, and continuously progresses with advancing age, until death.

While effective and sustainable weight loss is the primary driver behind the ketogenic diet’s surge, there is more to it than its ability to efficiently burn fat.   It’s been proven to help improve your risks of acquiring cardiovascular diseases, Alzheimer’s disease, help maintain muscle and hormone balance, helps manage PCOS, and even lower the risks of certain cancers. [1]   And,  the ketogenic diet may also improve the decline of DHEA. 

 

What is DHEA?

Again, it is one of the most abundant circulating steroids in the human body [2], that primarily serves as a precursor for androgens like testosterone, but also play a role in the production of estrogen.  Since it is associated with hormone production, low levels of the steroid are therefore linked to hormonal deficiencies. [3]  

 

DHEA the “Fountain of Youth” hormone

At birth, circulatory levels of the hormone are high.  However, they reach their highest values between the ages of 20-30 years, but concentrations steadily decline after that.  At the age of 70–80 years, peak concentrations are only 10–20% of those observed in 20-30 year-olds [2].   While the physiological and pathophysiological functions are not yet understood, one of the most popular descriptions considers it to be the “hormone of youth” as the long-term dynamics of DHEA levels are characterized by a sharp age-related decline.

Interestingly, concentrations correlate with longevity in healthy non-human primates, and some epidemiologic studies suggest that a similar relationship occurs in humans  [4].  Further, while an age-related decline in DHEA secretion by the adrenal cortex does not appear to affect other adrenal steroids,  its decline is nevertheless associated with age-related changes such as sarcopenia and osteopenia, atherosclerosis, gradual deterioration of the immune system, and cognitive impairment [5, 6, 7, 8, 9]. 

 

Other factors that contribute to low DHEA

While the most common and naturally occurring reason behind low DHEA is aging, there are many other contributing factors worth noting.

Diseases that may contribute to lower levels of the hormone include hypogonadism, type II diabetes, obesity, and thyroid disorders— conditions. [10]  However, current ketogenic diet research shows that the diet can positively impact patients with these diseases, which may further impact DHEA [13]. 

Other dietary factors may include a low-fat diet. In fact, a low-fat diet may not be optimal, as it may disrupt hormone regulation, resulting in low DHEA levels.  [11, 12]   While trans fats are largely considered unhealthy, other fats might actually improve hormone levels.  The body needs cholesterol to produce DHEA, and cholesterol to produce the hormone comes from dietary fat.   If you’re experiencing symptoms of low levels of DHEA, you may not be eating enough fat, and a high-fat low-carbohydrate ketogenic diet approach may improve your levels. 

A sedentary lifestyle is also correlated with low DHEA  [14].  The decreased muscle-building activity results in a lower amount of testosterone secretion, which affects the amount of DHEA produced as well.   Other lifestyle factors involved include poor sleep habits. Hormone production is optimized when sleep is optimized.  And, lack of sleep upregulates the production of the hormone cortisol, which has been found to negatively impact DHEA production as well.  [15]

 

Supplementing DHEA for testosterone

The most important function of supplementing DHEA is improving testosterone production, especially if you’re deficient. Supplementation could help delay the effects of age-related testosterone decline such as [16]:

 

  1. 1. Low sex drive
    2. Weakness and Depression
    3. Loss of muscle mass and bone density
    4. Erectile dysfunction
    5. Hair loss
    6. Low Semen Volume
    7. Redistribution of body fat
    8. Fatigue

 

While DHEA improves testosterone production,  and testosterone is considered a “male hormone,” low levels adversely affect women as well.  Other than the non-male exclusive symptoms, women could experience [16]:

 

1. Fertility issues
2. Vaginal Dryness
3. Irregular menstrual cycles
4. Decreased libido

 

Advantages of the Ketogenic Diet on DHEA

Some studies on patients with Rheumatoid Arthritis found that fasting and the ketogenic diet increased DHEA-S production significantly: a 34% increase in just a week from baseline (17).  

Further studies have shown that supplementation of the form 7-Keto DHEA , an oxygenated metabolite of DHEA, also has weight-loss enhancing effects when taken on a ketogenic diet.  Studies have shown that the metabolite increases the levels of the thyroid hormone T3, which helps to regulate your body’s metabolism.  Another randomized, double-blind, placebo-controlled study involving 30 subjects found that at the end of the eight-week study, the patients who were randomized to the metabolite lost an average of 6.34 pounds, while those receiving the placebo lost only 2.2 pounds [18, 19]. 

 

Why DHEA is not well-known or studied

In the past decade, however, few studies have concentrated on these physiological relationships, or on the role of exogenous DHEA supplementation, and dietary manipulation.  It would appear that more information on the ketogenic diet and its ability to improve DHEA levels in men and women would warrant further scientific study. 

However, DHEA is an endogenous metabolite that cannot be patented.  Therefore, the pharmaceutical industry may be reluctant to fund expensive human studies [20],   And, private and institutional sponsors may not be inclined to support further research because it is already commonly available as a nutraceutical.   For this reason,  it is difficult to suggest that the ketogenic diet will inevitably benefit the production of DHEA, but preliminary evidence suggests that it may.


References:

 

1. Paoli, A., Rubini, A., Volek, J. S., & Grimaldi, K. A. (2013). Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. European Journal of Clinical Nutrition, 67(8), 789–796. doi:10.1038/ejcn.2013.116

2.Rutkowski, K., Sowa, P., Rutkowska-Talipska, J., Kuryliszyn-Moskal, A., & Rutkowski, R. (2014). Dehydroepiandrosterone: Hypes and Hopes. Drugs, 74(11), 1195–1207. doi:10.1007/s40265-014-0259-8

3. Guay AT, Jacobson J. Decreased free testosterone and dehydroepiandrosterone-sulfate levels in women with decreased libido. J Sex Marital Ther. 2002;28 Suppl 1:129-42. 

4. Roth GS, Lane MA, Ingram DK, et al. Biomarkers of caloric restriction may predict longevity in humans. Science. 2002;297:811.

5. Traish, A. M., Kang, H. P., Saad, F., & Guay, A. T. (2011). Dehydroepiandrosterone— A Precursor Steroid or an Active Hormone in Human Physiology (CME). The Journal of Sexual Medicine, 8(11), 2960–2982. doi:10.1111/j.1743-6109.2011.02523.x 

6. Dhatariya, K. K., & Nair, K. S. (2003). Dehydroepiandrosterone: Is There a Role for Replacement? Mayo Clinic Proceedings, 78(10), 1257–1273. doi:10.4065/78.10.1257

7. Valenti, G. (2006). Consensus Document on substitution therapy with DHEA in the elderly. Aging Clinical and Experimental Research, 18(4), 277–300. doi:10.1007/bf03324662

8. Panjari, M., & Davis, S. R. (2007). Dehydroepiandrosterone therapy for women: effect on sexual function and wellbeing. Human Reproduction Update, 13(3), 239–248. doi:10.1093/humupd/dml055

9.  Orentreich N, Brind JL, Rizer RL., & Vogelman, J.H (1984).  Age Changes and Sex Differences in Serum Dehydroepiandrosterone Sulfate Concentrations throughout Adulthood. The Journal of Clinical Endocrinology & Metabolism, 59(3), 551–555. doi:10.1210/jcem-59-3-551 

10. Samaras N, Samaras D, Frangos E, Forster A, Philippe J. A review of age-related dehydroepiandrosterone decline and its association with well-known geriatric syndromes: is treatment beneficial?. Rejuvenation Res. 2013;16(4):285-94.

11. Hämäläinen, E. K., Adlercreutz, H., Puska, P., & Pietinen, P. (1983). Decrease of serum total and free testosterone during a low-fat high-fibre diet. Journal of Steroid Biochemistry, 18(3), 369–370. doi:10.1016/0022-4731(83)90117-6

12. Wang C, Catlin DH, Starcevic B, et al. Low-fat high-fiber diet decreased serum and urine androgens in men. J Clin Endocrinol Metab. 2005;90(6):3550-9.

13. Papierska, L. (2017). Adrenopause – does it really exist? Menopausal Review, 2, 57–60. doi:10.5114/pm.2017.68593

14. Hayes LD, Herbert P, Sculthorpe NF, Grace FM. Exercise training improves free testosterone in lifelong sedentary aging men. Endocr Connect. 2017;6(5):306-310.

15. Heaney JL, Carroll D, Phillips AC. Physical activity, life events stress, cortisol, and DHEA: preliminary findings that physical activity may buffer against the negative effects of stress. J Aging Phys Act. 2014;22(4):465-73.

16. Fouany MR, Sharara FI. Is there a role for Dehydroepiandrosterone supplementation in women with diminished ovarian reserve?. J Assist Reprod Genet. 2013;30(9):1239-44.

17. Fraser DA, Thoen J, Djøseland O, Førre O, Kjeldsen-kragh J. Serum levels of interleukin-6 and dehydroepiandrosterone sulphate in response to either fasting or a ketogenic diet in rheumatoid arthritis patients. Clin Exp Rheumatol. 2000;18(3):357-62.

18. Zenk JL, Frestedt JL, Kuskowski MA. HUM5007, a novel combination of thermogenic compounds, and 3-acetyl-7-oxo-dehydroepiandrosterone: each increases the resting metabolic rate of overweight adults. J Nutr Biochem. 2007;18(9):629-34.

19. Kaiman, D. S., Colker, C. M., Swain, M. A., Torina, G. C., & Shi, Q. (2000). A randomized, double-blind, placebo-controlled study of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy overweight adults. Current Therapeutic Research, 61(7), 435–442. doi:10.1016/s0011-393x(00)80026-0

20. Celec P, Sta´rka L. Dehydroepiandrosterone: is the fountain of youth drying out? Physiol Res. 2003;52:397–407.

 

 

 


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