When it comes to chronic diseases, the Big 3 are heart disease, cancer, and type 2 diabetes. Heart disease is the number one killer in the US, with cancer a close second. Diabetes numbers are increasing at an alarming rate.

I recently was reading several studies on one gene that surprisingly influences all three of these diseases. The gene is called ARNTL, but the protein that it codes for is BMAL1, which is how it is usually referred to in research papers.

BMAL1 Gene Function:

Our circadian clock is driven by a pair of genes that influence the daytime (CLOCK and BMAL1) and another pair of genes that govern the night half of the rhythm (PER and CRY).  During the day, BMAL1 and CLOCK levels rise; at night, PER’s and CRY’s levels peak.

When you read studies about circadian clock genes, you will see terminology like ‘period’ and ‘amplitude’. It is easier to picture this if you visual the amount of BMAL1 rising and falling like a sine wave:

Quite a lot of your body’s processes rise and fall over the course of the day. In fact, researchers estimate that 20 – 43% of genes are following a circadian pattern (depending on how they define it and which tissue they look at).

These circadian rhythms are obvious when you think about our natural sleep/wake cycle. Other biological rhythms include cortisol levels, body temperature, and blood pressure.

Blood pressure also follows a natural rhythm over the course of a 24-hour day, dipping by about 10% at night.[ref] Dipping seems to be important; people with high blood pressure often lose that oscillation. Studies on mice show that disrupting the natural dipping pattern will actually cause heart disease.[ref] Other studies found that BMAL1 genetic variants are linked to heart disease.[ref] And a recent study found that loss of BMAL1 causes atherosclerosis.[ref]

Light at night and working the night shift have both been tied to an increased risk in breast cancer. But not all studies show the same increase in risk, and genetic variants seem to play a role in whether light at night significantly increases your risk of breast cancer. BMAL1 gene variants have been tied to both increased[ref][ref] and decreased risk of cancer[ref], depending on the variant and type of cancer. One possible reason for this has been shown in a recent study that looked at what happens to cells when BMAL1 is deleted. The study found that in some types of cancer cells, deleting BMAL1 increased invasive cancer but in other cells, it triggered apoptosis which killed the cancer cell.[ref]

Several circadian genetic variants have been found to increase the risk of type 2 diabetes. Some, like melatonin receptor variants, influence insulin release and lead to insulin resistance for those who eat too late at night. BMAL1, on the other hand, is involved in pancreatic beta cell proliferation as well as regulation of adipogenesis (fat cell creation). [ref]


BMAL1 Genetic Variants

Check your 23andMe results for rs6486122 (v4, v5):

  • TT: increased risk of heart disease, diabetes [ref]
  • CT: increased risk of heart disease, diabetes
  • CC: normal / common type

Check your 23andMe results for rs11022775 (v4 only):

  • TT: Increased risk of diabetes [ref][ref]
  • CT: increased risk of diabetes
  • CC: normal / common type

Check your 23andMe results for rs969485 (v4, v5)

  • GG: increased risk of breast cancer with night shift work[ref]
  • AG:  increased risk of breast cancer with night shift work (64%)
  • AA: normal / common type

Check your 23andMe results for rs2278749 (v4, v5):

  • TT: night shift work less likely to increase breast cancer risk[ref] more fertile[ref]
  • CT: night shift work less likely to increase breast cancer risk[ref]
  • CC: normal / common type

Lifehacks

Circadian optimization is foundational. You need to block out blue light at night either through turning off electronics and bright overhead lights or through wearing blue-blocking glasses. Bright light during the day is also essential, so get outside first thing in the morning.

Selenium, a mineral found in Brazil nuts, has also been found to upregulate BMAL1 levels.[ref] You can eat Brazil nuts (only a couple a day should give you enough selenium) or there are inexpensive selenium supplements. Taking selenium first thing in the morning may give you the most benefit for increasing BMAL1.


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