December 2022

Friends:

From our previous discussion on the amino acids, we established that a particularly essential amino acid,  leucine, which is a branched amino acid, is crucial for not only muscle tissue health and growth but also in the presence of glucose stimulates insulin which in turn facilitates amino acid entry into muscles and makes them grow.

Moderately increasing dietary protein as we exercise and age has very positive findings as to the efficacy of this approach, but too much has negative effects on bones as well as increasing the ammonia load for the liver in the degradation of protein and ridding the body of excess nitrogenous wastes.

Peak muscle mass occurs between ages 20 and 35, declining gradually at age 40. Typically, men lose 20% of their muscle mass between ages 40 and 60.

The problem typically gets more progressive with age–primarily through changes in activity and less and less physical exercise. 

It is speculated that extra leucine, the anabolic trigger, might be valuable for slowing age-related muscle wasting.

Unfortunately, older adults show a blunted muscle protein synthesis (MPS) and anabolic resistance compared to younger adults. Recent research has suggested that anabolic resistance can be overcome by consuming greater quantities of leucine( and Vitamin D3) and let me emphasize, working out–especially resistance and antigravity exercise or weight-training ( no slacking!) is very key.

In a recent study, published in the Journal of Nutrition on July 1, 2018,  “it is confirmed that leucine and not the total protein content of a supplement is the primary determinant of muscle protein anabolic responses in healthy older women.” The study showed that “lower protein (10g  with extra leucine compared with a 25 g/ protein dose) induced similar increases in acute and integrated MPS in healthy older women.  Perhaps one can make the empathic statement that Lower-protein supplements with added leucine may represent an advantageous approach in older adults and seems to be a fair statement to make in maintaining skeletal muscle anabolic sensitivity and attenuating muscle loss; however, further work is needed using longer-term interventions.”

Fortunately,  leucine in foods is ubiquitous– also found in beer which is good for bones for additional reasons as well, coffee, mushrooms, microalgae,  and various grains, but what if one wants an efficient leucine boost without excessive food consumption? 

What if  I need to be on a lower protein diet but want the benefits offered in a higher protein diet?

An intriguing compound that has possibilities and feasibility for some, and is often promoted by bodybuilders and athletes for years,  is a very metabolically  active and natural form of leucine called HMB-Beta-hydroxy-beta-methyl butyrate (HMB) ‘

HMB is a metabolite of leucine and is the most we can break down leucine (that we know of). 

Just about 5% of leucine is broken down into HMB in our body and it is the main compound and form of leucine that stops the breakdown of muscle (also known as catabolism).

There is experimental evidence supporting that supplementation of this metabolite in the form of a supplement, plays a role in increased performance and muscle sparring, and hypertrophy, but this really depends on one’s total protein and total leucine in the diet and their general health and activity level.

An important point: For a protein to work optimally, both for muscles and bones,  a sizeable body of research emphasizes the role of higher Vitamin D3 levels.

It is always kind of a double take when one considers Vitamin D is actually a fully legitimate, mildly anabolic steroid hormone!

However, leucine even goes into more esoteric areas of function.

l-Kynurenine is a metabolite of the essential amino acid l-tryptophan used in the production of niacin. Kynurenine is synthesized by the enzyme tryptophan dioxygenase, which is made primarily but not exclusively in the liver,

The kynurenine pathway (KP) plays a critical role in generating cellular energy in the form of nicotinamide adenine dinucleotide (NAD+).  KP is a key regulator of the immune system. 

Perhaps more importantly in the context of psychiatry, many kynurenines are neuroactive, modulating neuroplasticity and/or exerting a neurotoxic effect. through their effects on neurotransmission and can influence moods and psychiatric states of health including depression. 

Leucine decreased brain kynurenine levels, blocked LPS-induced depression-like behavior, and had antidepressant-like effects in control mice. 

However, Leucine had no effect of its own on sickness behavior and neuroinflammation.

These findings demonstrate that leucine has antidepressant properties vis-à-vis inflammation-induced depression and one mechanism for this is by blocking the ability of kynurenine to enter the brain.

So just as you may think we have nailed down the story of leucine, here comes Parkinson’s Disease which appears to benefit from a LOWER  leucine and protein intake.

But we need to put this in context and this only becomes really relevant if one develops this unfortunate, usually progressive condition which often involves to various degrees,  a genetic mishandling of leucine.

What’s the practical takeaway as a recommendation?

It really depends on the individual and their own biological uniqueness, but with a broad brush stroke, I feel comfortable with the following sweeping generalization aimed at nutritional protein for healthy people:

1. A baseline of about 1 g/ kg body weight of excellent quality protein for most people.

2. If extremely athletic, teen growth spurts, and elderly, up to 1.2-2.0 g/ kg. 

As we age, less efficient with our MPS ( Muscle Protein Synthesis) so more protein to compensate.

3. In order to help with #2, protein supplementation is an excellent inclusion in the diet. 

Whey isolate is excellent as well as an option,  carefully formulated plant sources.

4. If digestive issues are a problem or do not do well on higher protein intake,  or plant sources are too limited, or perhaps you wish to push more of the anabolic results with MPS, or if you are quite elderly and wish to continue to train and workout,  or if you had a long or chronic illness or injury recovery,  or if very osteoporotic and fragile bones,   then I have no problem in adding HMB supplementation with extra Vitamin D3 ( 2000-6000 i.u. dally with Vitamin K2) as part of your strategically designed diet!

Continue to study, train,  see what works for you, and note, that it’s okay to adjust your protein intake up or down as your health and age should dictate–good luck!